Neurodegeneration and Dementia Flashcards

1
Q

name examples of diagnostic tools for dementia

A
  • neuroimaging (PET, MRI-volumetry)
  • CSF biomarkers
  • psychometric tests
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2
Q

outline the processes of the amyloid cascade (according to the amyloid hypothesis/theory)

A

APP cut by secretases → Ab-peptide → amyloid species → soluble oligomers (which are now considered to be synaptotoxic) → amyloid fibrillies → b-amyloid plaques → neuroinflammation → tau tangles

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3
Q

what are the two opposing theories on amyloid and tau pathology?

A
  • amyloid theory - tau is merely a result of the amyloid cascade, but is not a main cause of the disease
  • tau-protein theory - disturbed axonal transport and protein metabolism leads to amyloid plaques, which are not themselves essential to the disease
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4
Q

He et al., 2017 study on tau vs. amyloid development

A
  • mice injected with tau vs. amyloid
  • injecting amyloid led to tau tangles, but injecting tau did not lead to amyloid plaques
  • Ab-protein levels drop → amyloid plaques increase → tau tangles
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5
Q

describe subjective cognitive decline (SCD)

A
  • stage prior to MCI
  • identified with biomarkers, and patients start recognizing mild symptoms
  • the symptoms cannot yet be determined using psychometric tests
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6
Q

Alzheimer’s Disease genetics

A
  • APOE e4e4 increases the association between amyloid depositions and subsequent development of AD (homogenous APOE-4 carriers) - 90% risk of developing AD by the age of 90
  • APOE e2e4 increases the association between amyloid depositions and subsequent development of AD (heterogeneous APOE-4 carriers), but not as significantly as APOE e4e4
  • Familiar cases - mutations in three different genes, which subsequently increase the risk of developing AD
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7
Q

what are Amyloid-Related Imaging Abnormalities (ARIAs) and what kinds exist?

A
  • Imaging findings detected on MRI, which are associated with the investigational use of monoclonal antibodies targeting amyloid-β, including aducanumab
  • ARIA-H - hemosiderin deposits (small hemorrhages)
  • ARIA-E - cerebral edema (fluid accumulation)
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8
Q

main risk factors

A
  • non-degenerative dementias - high blood pressure, diabetes, depression, other lifestyle factors
  • degenerative dementias - old age is the main risk factor for neurodegenerative diseases causing dementia (+ genetics)
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9
Q

clinical trial outcomes

A
  • monoclonal antibody treatments
  • Aducanumab
  • Lecanemab - recently approved by FDA
  • not ideal for all patients, but effective for many (slows down disease progression - amyloid accumulation as well as symptom development for several months, up to 1.5y so far)
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